Low-dose irradiation of the gut improves the efficacy of PD-L1 blockade in metastatic cancer patients

Jianzhou Chen¹, Antonin Levy², Ai-Ling Tian³, Xuehan Huang⁴, Guoxin Cai³, Marine Fidelle⁵, Conrad Rauber⁶, Pierre Ly³, Eugénie Pizzato³, Lisa Sitterle⁷, Gianmarco Piccinno⁸, Peng Liu⁹, Sylvère Durand¹⁰, Misha Mao¹¹, Liwei Zhao⁹, Valerio Iebba¹², Hannah Felchle¹³, Anne-Laure Mallard de La Varende³, Julius Clemens Fischer¹³, Simon Thomas³, Tim F Greten¹⁴, Jennifer C Jones¹⁵, Cecilia Monge¹⁴, Sandra Demaria¹⁶, Silvia Formenti¹⁶, Lorenzo Belluomini¹⁷, Valeria Dionisi¹⁸, Christophe Massard¹⁹, Pierre Blanchard²⁰, Charlotte Robert⁷, Clément Quevrin⁷, Eloise Lopes⁷, Céline Clémenson⁷, Michele Mondini⁷, Lydia Meziani⁷, Yizhou Zhan⁴, Chengbing Zeng⁴, Qingxin Cai⁴, Daphne Morel²¹, Roger Sun², Pierre-Antoine Laurent², Monica Mangoni²², Vanessa Di Cataldo²³, Chiara Arilli²⁴, Maike Trommer²⁵, Simone Wegen²⁶, Sebastian Neppl²⁷, Rachel P Riechelmann²⁸, Marcos P Camandaroba²⁸, Elson Santos Neto²⁹, Pierre-Edouard Fournier³⁰, Nicola Segata³¹, Peter Holicek³², Lorenzo Galluzzi³³, Aitziber Buqué¹⁶, Carolina Alves Costa Silva³⁴, Lisa Derosa³⁵, Guido Kroemer³⁶, Chuangzhen Chen³⁷, Laurence Zitvogel³⁸, Eric Deutsch²

Affiliations

¹ Gustave Roussy Cancer Campus (GRCC), Clinicobiome, 94805 Villejuif Cedex, France; Faculté de Médecine, Université Paris-Saclay, 94270 Kremlin-Bicêtre, France; Institut National de la Santé Et de la Recherche Médicale (INSERM) UMR 1015, Equipe Labellisée-Ligue Nationale contre le Cancer, 94805 Villejuif, France; Department of Radiation Oncology, Cancer Hospital of Shantou University Medical College, Shantou 515031, China.
² Faculté de Médecine, Université Paris-Saclay, 94270 Kremlin-Bicêtre, France; Department of Radiation Oncology, Gustave Roussy Cancer Campus (GRCC), 94805 Villejuif, France; INSERM U1030, Radiothérapie Moléculaire et Innovations Thérapeutiques, Gustave Roussy Cancer Campus (GRCC), 94805 Villejuif, France.
³ Gustave Roussy Cancer Campus (GRCC), Clinicobiome, 94805 Villejuif Cedex, France; Faculté de Médecine, Université Paris-Saclay, 94270 Kremlin-Bicêtre, France; Institut National de la Santé Et de la Recherche Médicale (INSERM) UMR 1015, Equipe Labellisée-Ligue Nationale contre le Cancer, 94805 Villejuif, France.
⁴ Department of Radiation Oncology, Cancer Hospital of Shantou University Medical College, Shantou 515031, China.
⁵ Gustave Roussy Cancer Campus (GRCC), Clinicobiome, 94805 Villejuif Cedex, France; Institut National de la Santé Et de la Recherche Médicale (INSERM) UMR 1015, Equipe Labellisée-Ligue Nationale contre le Cancer, 94805 Villejuif, France; CICBT1428, Gustave Roussy Cancer Campus (GRCC), 94805 Villejuif, France.
⁶ Gustave Roussy Cancer Campus (GRCC), Clinicobiome, 94805 Villejuif Cedex, France; Faculté de Médecine, Université Paris-Saclay, 94270 Kremlin-Bicêtre, France; Institut National de la Santé Et de la Recherche Médicale (INSERM) UMR 1015, Equipe Labellisée-Ligue Nationale contre le Cancer, 94805 Villejuif, France; Department of Gastroenterology and Infectious Diseases, University Hospital Heidelberg, 69120 Heidelberg, Germany.
⁷ INSERM U1030, Radiothérapie Moléculaire et Innovations Thérapeutiques, Gustave Roussy Cancer Campus (GRCC), 94805 Villejuif, France.
⁸ Department of Computational, Cellular and Integrative Biology, University of Trento, 38123 Trento, Italy.
⁹ Metabolomics and Cell Biology Platforms, UMS AMMICa, Gustave Roussy Cancer Campus, 94805 Villejuif, France; Centre de Recherche des Cordeliers, INSERM U1138, Équipe Labellisée - Ligue Nationale contre le Cancer, Université Paris Cité, Sorbonne Université, 75006 Paris, France.
¹⁰ Metabolomics and Cell Biology Platforms, UMS AMMICa, Gustave Roussy Cancer Campus, 94805 Villejuif, France.
¹¹ Metabolomics and Cell Biology Platforms, UMS AMMICa, Gustave Roussy Cancer Campus, 94805 Villejuif, France; Centre de Recherche des Cordeliers, INSERM U1138, Équipe Labellisée - Ligue Nationale contre le Cancer, Université Paris Cité, Sorbonne Université, 75006 Paris, France; General Surgery, Cancer Center, Department of Breast Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang 310014, China; Zhejiang University, Hangzhou, Zhejiang 310000, China.
¹² Gustave Roussy Cancer Campus (GRCC), Clinicobiome, 94805 Villejuif Cedex, France.
¹³ Metabolomics and Cell Biology Platforms, UMS AMMICa, Gustave Roussy Cancer Campus, 94805 Villejuif, France; Centre de Recherche des Cordeliers, INSERM U1138, Équipe Labellisée - Ligue Nationale contre le Cancer, Université Paris Cité, Sorbonne Université, 75006 Paris, France; Technical University of Munich (TUM), TUM School of Medicine and Health, Klinikum rechts der Isar, Department of Radiation Oncology, 81675 Munich, Germany.
¹⁴ Gastrointestinal Malignancy Section, Thoracic and Gastrointestinal Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
¹⁵ Translational Nanobiology Section, Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA; Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
¹⁶ Department of Radiation Oncology, Weill Cornell Medicine, New York, NY 10065, USA.
¹⁷ Section of Innovation Biomedicine - Oncology Area, Department of Engineering for Innovation Medicine (DIMI), University of Verona and University and Hospital Trust (AOUI) of Verona, 37134 Verona, Italy.
¹⁸ Department of Radiation Oncology, University of Verona Hospital Trust, 37126 Verona, Italy.
¹⁹ Faculté de Médecine, Université Paris-Saclay, 94270 Kremlin-Bicêtre, France; INSERM U1030, Radiothérapie Moléculaire et Innovations Thérapeutiques, Gustave Roussy Cancer Campus (GRCC), 94805 Villejuif, France; Drug Development Department (DITEP), Gustave Roussy Cancer Campus, 94805 Villejuif, France.
²⁰ Faculté de Médecine, Université Paris-Saclay, 94270 Kremlin-Bicêtre, France; INSERM U1030, Radiothérapie Moléculaire et Innovations Thérapeutiques, Gustave Roussy Cancer Campus (GRCC), 94805 Villejuif, France.
²¹ Department of Radiation Oncology, Gustave Roussy Cancer Campus (GRCC), 94805 Villejuif, France; INSERM U1030, Radiothérapie Moléculaire et Innovations Thérapeutiques, Gustave Roussy Cancer Campus (GRCC), 94805 Villejuif, France.
²² Radiotherapy Unit, Department of Experimental and Clinical Biomedical Sciences"Mario Serio" University of Florence, 50134 Florence, Italy.
²³ Radiation Oncology Unit, Azienda Ospedaliero Universitaria Careggi, 50134 Florence, Italy.
²⁴ Medical Physics Unit, Azienda Ospedaliero-Universitaria Careggi, 50134 Florence, Italy.
²⁵ Department of Radiation Oncology, Cyberknife and Radiotherapy, Faculty of Medicine and University Hospital Cologne, 50937 Cologne, Germany; Center for Integrated Oncology (CIO), Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany; Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany; Olivia Newton-John Cancer Wellness & Research Centre, Austin Health, Department of Radiation Oncology, Heidelberg VIC 3084, Melbourne, Australia.
²⁶ Department of Radiation Oncology, Cyberknife and Radiotherapy, Faculty of Medicine and University Hospital Cologne, 50937 Cologne, Germany; Center for Integrated Oncology (CIO), Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany.
²⁷ Department of Radiation Oncology, Cyberknife and Radiotherapy, Faculty of Medicine and University Hospital Cologne, 50937 Cologne, Germany.
²⁸ Department of Clinical Oncology, AC Camargo Cancer Center, São Paulo 01509-900, Brazil.
²⁹ Department of Radiation Oncology, AC Camargo Cancer Center, São Paulo 01509-001, Brazil.
³⁰ IHU Méditerranée Infection, 13005 Marseille, France.
³¹ Department of Computational, Cellular and Integrative Biology, University of Trento, 38123 Trento, Italy; IEO, Istituto Europeo di Oncologia IRCCS, 20139 Milan, Italy.
³² Department of Radiation Oncology, Weill Cornell Medicine, New York, NY 10065, USA; Sotio Biotech, 19000 Prague, Czech Republic.
³³ Cancer Signaling and Microenvironment Program, Fox Chase Cancer Center, Philadelphia, PA 19111-2497, USA.
³⁴ Gustave Roussy Cancer Campus (GRCC), Clinicobiome, 94805 Villejuif Cedex, France; Institut National de la Santé Et de la Recherche Médicale (INSERM) UMR 1015, Equipe Labellisée-Ligue Nationale contre le Cancer, 94805 Villejuif, France.
³⁵ Gustave Roussy Cancer Campus (GRCC), Clinicobiome, 94805 Villejuif Cedex, France; Faculté de Médecine, Université Paris-Saclay, 94270 Kremlin-Bicêtre, France; Institut National de la Santé Et de la Recherche Médicale (INSERM) UMR 1015, Equipe Labellisée-Ligue Nationale contre le Cancer, 94805 Villejuif, France; CICBT1428, Gustave Roussy Cancer Campus (GRCC), 94805 Villejuif, France.
³⁶ Metabolomics and Cell Biology Platforms, UMS AMMICa, Gustave Roussy Cancer Campus, 94805 Villejuif, France; Centre de Recherche des Cordeliers, INSERM U1138, Équipe Labellisée - Ligue Nationale contre le Cancer, Université Paris Cité, Sorbonne Université, 75006 Paris, France; Institut du Cancer Paris CARPEM, Department of Biology, Hôpital Européen Georges Pompidou, AP-HP, 75015 Paris, France.
³⁷ Department of Radiation Oncology, Cancer Hospital of Shantou University Medical College, Shantou 515031, China. Electronic address: czchen2@stu.edu.cn.
³⁸ Gustave Roussy Cancer Campus (GRCC), Clinicobiome, 94805 Villejuif Cedex, France; Faculté de Médecine, Université Paris-Saclay, 94270 Kremlin-Bicêtre, France; Institut National de la Santé Et de la Recherche Médicale (INSERM) UMR 1015, Equipe Labellisée-Ligue Nationale contre le Cancer, 94805 Villejuif, France; CICBT1428, Gustave Roussy Cancer Campus (GRCC), 94805 Villejuif, France. Electronic address: Laurence.zitvogel@gustaveroussy.fr.

PMID: 40068595
PMCID: PMC11907695 (available on 2026-03-10)
DOI: 10.1016/j.ccell.2025.02.010

Low-dose irradiation of the gut improves the efficacy of PD-L1 blockade in metastatic cancer patients

Jianzhou Chen et al. Cancer Cell. 2025.

. 2025 Mar 10;43(3):361-379.e10.

doi: 10.1016/j.ccell.2025.02.010.

Authors

Affiliations

¹ Gustave Roussy Cancer Campus (GRCC), Clinicobiome, 94805 Villejuif Cedex, France; Faculté de Médecine, Université Paris-Saclay, 94270 Kremlin-Bicêtre, France; Institut National de la Santé Et de la Recherche Médicale (INSERM) UMR 1015, Equipe Labellisée-Ligue Nationale contre le Cancer, 94805 Villejuif, France; Department of Radiation Oncology, Cancer Hospital of Shantou University Medical College, Shantou 515031, China.
² Faculté de Médecine, Université Paris-Saclay, 94270 Kremlin-Bicêtre, France; Department of Radiation Oncology, Gustave Roussy Cancer Campus (GRCC), 94805 Villejuif, France; INSERM U1030, Radiothérapie Moléculaire et Innovations Thérapeutiques, Gustave Roussy Cancer Campus (GRCC), 94805 Villejuif, France.
³ Gustave Roussy Cancer Campus (GRCC), Clinicobiome, 94805 Villejuif Cedex, France; Faculté de Médecine, Université Paris-Saclay, 94270 Kremlin-Bicêtre, France; Institut National de la Santé Et de la Recherche Médicale (INSERM) UMR 1015, Equipe Labellisée-Ligue Nationale contre le Cancer, 94805 Villejuif, France.
⁴ Department of Radiation Oncology, Cancer Hospital of Shantou University Medical College, Shantou 515031, China.
⁵ Gustave Roussy Cancer Campus (GRCC), Clinicobiome, 94805 Villejuif Cedex, France; Institut National de la Santé Et de la Recherche Médicale (INSERM) UMR 1015, Equipe Labellisée-Ligue Nationale contre le Cancer, 94805 Villejuif, France; CICBT1428, Gustave Roussy Cancer Campus (GRCC), 94805 Villejuif, France.
⁶ Gustave Roussy Cancer Campus (GRCC), Clinicobiome, 94805 Villejuif Cedex, France; Faculté de Médecine, Université Paris-Saclay, 94270 Kremlin-Bicêtre, France; Institut National de la Santé Et de la Recherche Médicale (INSERM) UMR 1015, Equipe Labellisée-Ligue Nationale contre le Cancer, 94805 Villejuif, France; Department of Gastroenterology and Infectious Diseases, University Hospital Heidelberg, 69120 Heidelberg, Germany.
⁷ INSERM U1030, Radiothérapie Moléculaire et Innovations Thérapeutiques, Gustave Roussy Cancer Campus (GRCC), 94805 Villejuif, France.
⁸ Department of Computational, Cellular and Integrative Biology, University of Trento, 38123 Trento, Italy.
⁹ Metabolomics and Cell Biology Platforms, UMS AMMICa, Gustave Roussy Cancer Campus, 94805 Villejuif, France; Centre de Recherche des Cordeliers, INSERM U1138, Équipe Labellisée - Ligue Nationale contre le Cancer, Université Paris Cité, Sorbonne Université, 75006 Paris, France.
¹⁰ Metabolomics and Cell Biology Platforms, UMS AMMICa, Gustave Roussy Cancer Campus, 94805 Villejuif, France.
¹¹ Metabolomics and Cell Biology Platforms, UMS AMMICa, Gustave Roussy Cancer Campus, 94805 Villejuif, France; Centre de Recherche des Cordeliers, INSERM U1138, Équipe Labellisée - Ligue Nationale contre le Cancer, Université Paris Cité, Sorbonne Université, 75006 Paris, France; General Surgery, Cancer Center, Department of Breast Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang 310014, China; Zhejiang University, Hangzhou, Zhejiang 310000, China.
¹² Gustave Roussy Cancer Campus (GRCC), Clinicobiome, 94805 Villejuif Cedex, France.
¹³ Metabolomics and Cell Biology Platforms, UMS AMMICa, Gustave Roussy Cancer Campus, 94805 Villejuif, France; Centre de Recherche des Cordeliers, INSERM U1138, Équipe Labellisée - Ligue Nationale contre le Cancer, Université Paris Cité, Sorbonne Université, 75006 Paris, France; Technical University of Munich (TUM), TUM School of Medicine and Health, Klinikum rechts der Isar, Department of Radiation Oncology, 81675 Munich, Germany.
¹⁴ Gastrointestinal Malignancy Section, Thoracic and Gastrointestinal Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
¹⁵ Translational Nanobiology Section, Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA; Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
¹⁶ Department of Radiation Oncology, Weill Cornell Medicine, New York, NY 10065, USA.
¹⁷ Section of Innovation Biomedicine - Oncology Area, Department of Engineering for Innovation Medicine (DIMI), University of Verona and University and Hospital Trust (AOUI) of Verona, 37134 Verona, Italy.
¹⁸ Department of Radiation Oncology, University of Verona Hospital Trust, 37126 Verona, Italy.
¹⁹ Faculté de Médecine, Université Paris-Saclay, 94270 Kremlin-Bicêtre, France; INSERM U1030, Radiothérapie Moléculaire et Innovations Thérapeutiques, Gustave Roussy Cancer Campus (GRCC), 94805 Villejuif, France; Drug Development Department (DITEP), Gustave Roussy Cancer Campus, 94805 Villejuif, France.
²⁰ Faculté de Médecine, Université Paris-Saclay, 94270 Kremlin-Bicêtre, France; INSERM U1030, Radiothérapie Moléculaire et Innovations Thérapeutiques, Gustave Roussy Cancer Campus (GRCC), 94805 Villejuif, France.
²¹ Department of Radiation Oncology, Gustave Roussy Cancer Campus (GRCC), 94805 Villejuif, France; INSERM U1030, Radiothérapie Moléculaire et Innovations Thérapeutiques, Gustave Roussy Cancer Campus (GRCC), 94805 Villejuif, France.
²² Radiotherapy Unit, Department of Experimental and Clinical Biomedical Sciences"Mario Serio" University of Florence, 50134 Florence, Italy.
²³ Radiation Oncology Unit, Azienda Ospedaliero Universitaria Careggi, 50134 Florence, Italy.
²⁴ Medical Physics Unit, Azienda Ospedaliero-Universitaria Careggi, 50134 Florence, Italy.
²⁵ Department of Radiation Oncology, Cyberknife and Radiotherapy, Faculty of Medicine and University Hospital Cologne, 50937 Cologne, Germany; Center for Integrated Oncology (CIO), Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany; Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany; Olivia Newton-John Cancer Wellness & Research Centre, Austin Health, Department of Radiation Oncology, Heidelberg VIC 3084, Melbourne, Australia.
²⁶ Department of Radiation Oncology, Cyberknife and Radiotherapy, Faculty of Medicine and University Hospital Cologne, 50937 Cologne, Germany; Center for Integrated Oncology (CIO), Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany.
²⁷ Department of Radiation Oncology, Cyberknife and Radiotherapy, Faculty of Medicine and University Hospital Cologne, 50937 Cologne, Germany.
²⁸ Department of Clinical Oncology, AC Camargo Cancer Center, São Paulo 01509-900, Brazil.
²⁹ Department of Radiation Oncology, AC Camargo Cancer Center, São Paulo 01509-001, Brazil.
³⁰ IHU Méditerranée Infection, 13005 Marseille, France.
³¹ Department of Computational, Cellular and Integrative Biology, University of Trento, 38123 Trento, Italy; IEO, Istituto Europeo di Oncologia IRCCS, 20139 Milan, Italy.
³² Department of Radiation Oncology, Weill Cornell Medicine, New York, NY 10065, USA; Sotio Biotech, 19000 Prague, Czech Republic.
³³ Cancer Signaling and Microenvironment Program, Fox Chase Cancer Center, Philadelphia, PA 19111-2497, USA.
³⁴ Gustave Roussy Cancer Campus (GRCC), Clinicobiome, 94805 Villejuif Cedex, France; Institut National de la Santé Et de la Recherche Médicale (INSERM) UMR 1015, Equipe Labellisée-Ligue Nationale contre le Cancer, 94805 Villejuif, France.
³⁵ Gustave Roussy Cancer Campus (GRCC), Clinicobiome, 94805 Villejuif Cedex, France; Faculté de Médecine, Université Paris-Saclay, 94270 Kremlin-Bicêtre, France; Institut National de la Santé Et de la Recherche Médicale (INSERM) UMR 1015, Equipe Labellisée-Ligue Nationale contre le Cancer, 94805 Villejuif, France; CICBT1428, Gustave Roussy Cancer Campus (GRCC), 94805 Villejuif, France.
³⁶ Metabolomics and Cell Biology Platforms, UMS AMMICa, Gustave Roussy Cancer Campus, 94805 Villejuif, France; Centre de Recherche des Cordeliers, INSERM U1138, Équipe Labellisée - Ligue Nationale contre le Cancer, Université Paris Cité, Sorbonne Université, 75006 Paris, France; Institut du Cancer Paris CARPEM, Department of Biology, Hôpital Européen Georges Pompidou, AP-HP, 75015 Paris, France.
³⁷ Department of Radiation Oncology, Cancer Hospital of Shantou University Medical College, Shantou 515031, China. Electronic address: czchen2@stu.edu.cn.
³⁸ Gustave Roussy Cancer Campus (GRCC), Clinicobiome, 94805 Villejuif Cedex, France; Faculté de Médecine, Université Paris-Saclay, 94270 Kremlin-Bicêtre, France; Institut National de la Santé Et de la Recherche Médicale (INSERM) UMR 1015, Equipe Labellisée-Ligue Nationale contre le Cancer, 94805 Villejuif, France; CICBT1428, Gustave Roussy Cancer Campus (GRCC), 94805 Villejuif, France. Electronic address: Laurence.zitvogel@gustaveroussy.fr.

PMID: 40068595
PMCID: PMC11907695 (available on 2026-03-10)
DOI: 10.1016/j.ccell.2025.02.010

Abstract

The mechanisms governing the abscopal effects of local radiotherapy in cancer patients remain an open conundrum. Here, we show that off-target intestinal low-dose irradiation (ILDR) increases the clinical benefits of immune checkpoint inhibitors or chemotherapy in eight retrospective cohorts of cancer patients and in tumor-bearing mice. The abscopal effects of ILDR depend on dosimetry (≥1 and ≤3 Gy) and on the metabolic and immune host-microbiota interaction at baseline allowing CD8⁺ T cell activation without exhaustion. Various strains of Christensenella minuta selectively boost the anti-cancer efficacy of ILDR and PD-L1 blockade, allowing emigration of intestinal PD-L1-expressing dendritic cells to tumor-draining lymph nodes. An interventional phase 2 study provides the proof-of-concept that ILDR can circumvent resistance to first- or second-line immunotherapy in cancer patients. Prospective clinical trials are warranted to define optimal dosimetry and indications for ILDR to maximize its therapeutic potential.

Keywords: Christensenella minuta; bile acids; cancer; dendritic cells; gut microbiota; metabolomics; radiotherapy; tumor immunosurveillance.

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Conflict of interest statement

Declaration of interests L. Zitvogel founded EverImmune and is the SAB president of EverImmune. L. Zitvogel had grant support from Daichi Sankyo, Kaleido, 9 m, and Pileje. G.K. has been holding research contracts with Daiichi Sankyo, Eleor, Kaleido, Lytix Pharma, PharmaMar, Osasuna Therapeutics, Samsara Therapeutics, Sanofi, Sutro, Tollys, and Vascage. G.K. is on the Board of Directors of the Bristol Myers Squibb Foundation France. G.K. is a scientific co-founder of EverImmune, Osasuna Therapeutics, Samsara Therapeutics, and Therafast Bio. G.K. is in the scientific advisory boards of Hevolution and Institut Servier. G.K. is the inventor of patents covering therapeutic targeting of aging, cancer, cystic fibrosis, and metabolic disorders. G.K.’s brother, Romano Kroemer, was an employee of Sanofi and now consults for Boehringer-Ingelheim. E.D. received grants from IMCORE/Roche Genentech, grants and personal fees from Boehringer, grants from Astrazeneca, grants and personal fees from Merck Serono, grants from BMS, and grants from MSD. E.D. is founder of Graegis pharmaceuticals. A.L. reports sponsored academic research at Gustave Roussy Cancer Center by Amgen, AstraZeneca, Beigene, F. Hoffmann-La Roche, and Pharmamar. C. Massard received consultant/advisory fees from Amgen, Astellas, Astra Zeneca, Bayer, BeiGene, BMS, Celgene, Debiopharm, Genentech, Ipsen, Janssen, Lilly, MedImmune, MSD, Novartis, Pfizer, Roche, Sanofi, and Orion. C. Massard is principal/sub-investigator of Clinical Trials for Abbvie, Aduro, Agios, Amgen, Argen-x, Astex, AstraZeneca, Aveo pharmaceuticals, Bayer, Beigene, Blueprint, BMS, Boeringer Ingelheim, Celgene, Chugai, Clovis, Daiichi Sankyo, Debiopharm, Eisai, Eos, Exelixis, Forma, Gamamabs, Genentech, Gortec, GSK, H3 biomedecine, Incyte, Innate Pharma, Janssen, Kura Oncology, Kyowa, Lilly, Loxo, Lysarc, Lytix Biopharma, Medimmune, Menarini, Merus, MSD, Nanobiotix, Nektar Therapeutics, Novartis, Octimet, Oncoethix, Oncopeptides AB, Orion, Pfizer, Pharmamar, Pierre Fabre, Roche, Sanofi, Servier, Sierra Oncology, Taiho, Takeda, Tesaro, Xencor. L.G. is/has been holding research contracts with Lytix Biopharma, Promontory and Onxeo, has received consulting/advisory honoraria from Boehringer Ingelheim, AstraZeneca, OmniSEQ, Onxeo, The Longevity Labs, Inzen, Imvax, Sotio, Promontory, Noxopharm, EduCom, and the Luke Heller TECPR2 Foundation, and holds Promontory stock options. L.D. is an SAB member of EverImmune. S. Demaria has received compensation for consultant/advisory services from Lytix Biopharma, EMD Serono, Ono Pharmaceutical, Genentech, and Johnson & Johnson Enterprise Innovati on Inc., and research support from Lytix Biopharma, Nanobiotix and Boehringer-Ingelheim for unrelated projects. L.B. received speakers’ fees from AstraZeneca, Merck Sharp & Dohme, Takeda, BMS and Roche, outside the submitted manuscript, travel fees from Takeda and Sanofi. R.S. received an ESMO Baselga Fellowship sponsored by Astrazeneca.

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Low-dose irradiation of the gut improves the efficacy of PD-L1 blockade in metastatic cancer patients

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Low-dose irradiation of the gut improves the efficacy of PD-L1 blockade in metastatic cancer patients

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Conflict of interest statement

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